Earlier developments of new methods for correlating proton chemical shifts with shifts of low-gamma nuclei have been continued. For the first time, it has been shown possible to record proton-carbon and proton-nitrogen shift correlation of small proteins (greater than 15 kD) at natural isotopic abundance. A quite different approach has been developed for correlating proton and phosphorous chemical shifts and applied to the study of oligonucleotides. New methods have been developed for recording phase-sensitive two-dimensional proton NMR spectra in water solution without the need for presaturation. In contrast to existing techniques, the new methods accomplish the water suppression in two stages: in the first stage a relatively low suppression is obtained, sufficient to overcome dynamic range problems in the receiver, in the second stage cycling removes the water signal from the spectrum almost completely. The new methods have been demonstrated for the important NOE, spin-locked NOE and homonuclear Hartmann- Hahn experiments. A new procedure has been developed for measurements of previously unresolvable coupling constants. By suppressing the effect of all scalar couplings apart from the interaction of interest in a two-dimensional experiment it becomes possible to extract the coupling constants of interest. The procedure has been applied to measurement of J(C3'H-O-P) couplings in the oligonucleotide d(CGCGAATTCGCG)2. The corresponding dihedral epsilon angles show significant differences with X-ray crystallographic work.